新产品编号:259957
2-(2-((4-氯苯基)硫代)乙氧基)-3-甲氧基-5-((2S,5S)-5-(3,4,5-三甲氧基苯基)四氢呋喃-2-基)苯并腈 Chemical Name: (?-trans-2-[2-(4-Chlorophenylsulfanyl)ethoxy]-3-methoxy-5-[5-(3,4,5-trimethoxyphenyl)tetrahydrofuran-2-yl]benzonitrile
CAS No. 193739-32-1, 205654-34-8 ((S,S)-isomer)
项目整合开发状态: Biological Testing
项目研究机构: CytoMed (Originator)
合成路线:Alkylation of 5-iodovanillin (I) with iodoethanol gave hydroxyethyl ether (II).This was condensed with vinyl ketone (III) in the presence of the thiazolium salt (IV) to produce the 1,4-diketone (V).Subsequent reduction of (V) with NaBH4 afforded 1,4-diol (VI),which was cyclized with trifluoroacetic acid in chloroform to furnish a mixture of cis and trans diaryltetrahydrofurans.The required trans isomer (VII) was isolated by column chromatography,and then treated with methanesulfonyl chloride and triethylamine to give mesylate (VIII).Further condensation of (VIII) with 4-chlorothiophenol (IX) provided sulfide (X).Finally,displacement of the iodine atom with CuCN in boiling DMF produced the title nitrile.
📌 参考资料/链接：
参考文献标题:(+-)-trans-2-[3-Methoxy-4-(4-chlorophenylthioethoxy)-5-(N-methyl-N-hydroxyureidyl)methylphenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (CMI-392),a potent dual 5-lipoxygenase inhibitor and platelet-activating factor receptor antagonist
文献作者:Cai,X.; Scannell,R.T.; Yaeger,D.; Hussoin,M.S.; Killian,D.B.; Qian,C.; Eckman,J.; Hwang,S.B.; Libertine-Garahan,L.; Yeh,C.G.; Ip,S.H.; Shen,T.Y.
参考来源:J Med Chem 1998,41(11),1970
📄 详细内容
合成路线:In a related procedure,iodination of acetophenone (XI) gave (XII).Subsequent alkylation of (XII) with dibromoethane afforded bromoethyl ether (XIII),which was converted to sulfide (XIV) by condensation with 4-chlorothiophenol (IX).Mannich reaction of (XIV) with paraformaldehyde and dimethylamine hydrochloride produced tertiary amine (XV),which was quaternized to (XVI) with MeI.Elimination in the resulting ammonium salt (XVI) produced vinyl ketone (XVII).Diketone (XIX) was then obtained by condensation with trimethoxybenzaldehyde (XVIII) in the presence of thiazolium salt (IV).Reduction of both ketone groups of (XIX) using NaBH4 yielded diol (XX),which was further cyclized with orthophosphoric acid in refluxing benzene to furnish a diastereomeric mixture of cis and trans diaryltetrahydrofurans (XXI).Iodine displacement in (XXI) with CuCN produced the corresponding diastereomeric mixture of cyanides,from which the target trans isomer was isolated by column chromatography.
参考文献标题:(?-Trans-2-[3-methoxy-4-(4-chlorophenyl thioethoxy)-5-cyanophenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran,a potent PAF-receptor antagonist
文献作者:Ram,B.; et al.
参考来源:Tetrahedron 1999,55(33),10163
产品链接: CAS No.205654-34-8››